Gaining MOMENTUM in Myelofibrosis Therapy

Primary myelofibrosis and myelofibrosis evolving from polycythemia vera or essential thrombocytosis are characterized by Janus kinase (JAK) mutations that activate JAK signaling pathways; treatment with available JAK inhibitors can improve splenic volume and symptoms but has no impact on or may worsen anemia. Momelotinib is an investigational oral JAK inhibitor that also inhibits activin A receptor type 1, a regulator of iron metabolism. Investigators conducted an industry-sponsored, multicenter, double-blind phase 3 trial (MOMENTUM) comparing momelotinib to danazol, an androgen with erythropoietic stimulating activity.

A total of 195 patients with myelofibrosis and anemia who previously received treatment with an approved JAK inhibitor were randomized 2:1 to momelotinib (200 mg once per day) plus placebo or danazol (300 mg twice per day) plus placebo. Assessment at 24 weeks included unblinding of treatment arm, with patients eligible to continue current treatment if they were responding or to cross over from danazol to momelotinib.

The primary endpoint — a 50% or better improvement in total symptom score at week 24 compared with baseline — was achieved by significantly more patients in the momelotinib arm than the danazol arm (25% vs. 9%; P=0.0095). Secondary outcomes, including hemoglobin level and splenic volume response assessed by computed tomography or magnetic resonance imaging, were also significantly improved with momelotinib; 35% of momelotinib recipients versus 17% of danazol recipients received no red cell transfusions through week 24. Overall survival trended in favor of momelotinib.

Side effects, including diarrhea, nausea, and asthenia, were mostly grade 1–2 and were more frequent with momelotinib; anemia was less frequent with momelotinib than with danazol, while frequency of neutropenia and thrombocytopenia did not differ between groups. Patients who crossed over from danazol to momelotinib had further improvements in hemoglobin levels.